ArticleThe Journal of biological chemistry2013
Plekhg4 is a novel Dbl family guanine nucleotide exchange factor protein for rho family GTPases.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- PLEKHG2 and the PLEKHG family: Linking Rho family GTPases to neural development and disorders.Histology and histopathology · 2025Review
- Benzene metabolites increase vascular permeability by activating heat shock proteins and Rho GTPases.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Direct and indirect regulation of β-glucocerebrosidase by the transcription factors USF2 and ONECUT2.NPJ Parkinson's disease · 2024Article
- Review
- Roles of the Dbl family of RhoGEFs in mechanotransduction - a review.Frontiers in cell and developmental biology · 2024Review
- Pleckstrin homology and RhoGEF domain containing G4 (PLEKHG4) leads to the activation of RhoGTPases promoting the malignant phenotypes of thyroid cancer.Apoptosis : an international journal on programmed cell death · 2023Article
- Canine Somatic Mutations from Whole-Exome Sequencing of B-Cell Lymphomas in Six Canine Breeds-A Preliminary Study.Animals : an open access journal from MDPI · 2023Article
- Review
- MicroRNA Regulation of the Small Rho GTPase Regulators-Complexities and Opportunities in Targeting Cancer Metastasis.Cancers · 2020Review
- Regulators of Rho GTPases in the Nervous System: Molecular Implication in Axon Guidance and Neurological Disorders.International journal of molecular sciences · 2019Review
- Low Electric Treatment activates Rho GTPase via Heat Shock Protein 90 and Protein Kinase C for Intracellular Delivery of siRNA.Scientific reports · 2019Article
- ZIKV - CDB: A Collaborative Database to Guide Research Linking SncRNAs and ZIKA Virus Disease Symptoms.PLoS neglected tropical diseases · 2016Article
- Article
- Hsc70 chaperone activity underlies Trio GEF function in axon growth and guidance induced by netrin-1.The Journal of cell biology · 2015Article
- Article
- Identification of novel mutations in Mexican patients with Aarskog-Scott syndrome.Molecular genetics & genomic medicine · 2015Article
- Regulating Rac in the nervous system: molecular function and disease implication of Rac GEFs and GAPs.BioMed research international · 2015Review
- Molecular mechanisms for the regulation of insulin-stimulated glucose uptake by small guanosine triphosphatases in skeletal muscle and adipocytes.International journal of molecular sciences · 2014Review
- The emerging role of guanine nucleotide exchange factors in ALS and other neurodegenerative diseases.Frontiers in cellular neuroscience · 2014Review
- Rho GAPs and GEFs: controling switches in endothelial cell adhesion.Cell adhesion & migration · 2014Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the PLEKHG4 (puratrophin-1) gene are associated with the heritable neurological disorder autosomal dominant spinocerebellar ataxia. However, the biochemical functions of this gene product have not been described. We report here that expression of Plekhg4 in the murine brain is developmentally regulated, with pronounced expression in the newborn midbrain and brainstem that wanes with age and maximal expression in the cerebellar Purkinje neurons in adulthood. We show that Plekhg4 is subject to ubiquitination and proteasomal degradation, and its steady-state expression levels are regulated by the chaperones Hsc70 and Hsp90 and by the ubiquitin ligase CHIP. On the functional level, we demonstrate that Plekhg4 functions as a bona fide guanine nucleotide exchange factor (GEF) that facilitates activation of the small GTPases Rac1, Cdc42, and RhoA. Overexpression of Plekhg4 in NIH3T3 cells induces rearrangements of the actin cytoskeleton, specifically enhanced formation of lamellopodia and fillopodia. These findings indicate that Plekhg4 is an aggregation-prone member of the Dbl family GEFs and that regulation of GTPase signaling is critical for proper cerebellar function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.